Critical care explorations最新文献

Objectives: To determine the actual cost and drivers of the cost of an extracorporeal cardiopulmonary resuscitation (E-CPR) care cycle.

Perspective: A time-driven activity-based costing study conducted from a healthcare provider perspective.

Setting: A quaternary care ICU providing around-the-clock E-CPR service for out-of-hospital cardiac arrest (OHCA) and in-hospital cardiac arrest (IHCA) in Australia.

Methods: The E-CPR care cycle was defined as the time from initiating E-CPR to hospital discharge or death of the patient. Detailed process maps with discrete steps and probabilistic decision nodes accounting for the complex trajectories of E-CPR patients were developed. Data about clinical and nonclinical resources and timing of activities was collected multiple times for each process . Total direct costs were calculated using the time estimates and unit costs per resource for all clinical and nonclinical resources. The total direct costs were combined with indirect costs to obtain the total cost of E-CPR.

Results: From 10 E-CPR care cycles observed during the study period, a minimum of 3 observations were obtained per process. The E-CPR care cycle's mean (95% CI) cost was $75,014 ($66,209-83,222). Initiation of extracorporeal membrane oxygenation (ECMO) and ECMO management constituted 18% of costs. The ICU management (35%) and surgical costs (20%) were the primary cost determinants. IHCA had a higher mean (95% CI) cost than OHCA ($87,940 [75,372-100,570] vs. 62,595 [53,994-71,890], p < 0.01), mainly because of the increased survival and ICU length of stay of patients with IHCA. The mean cost for each E-CPR survivor was $129,503 ($112,422-147,224).

Conclusions: Significant costs are associated with E-CPR for refractory cardiac arrest. The cost of E-CPR for IHCA was higher compared with the cost of E-CPR for OHCA. The major determinants of the E-CPR costs were ICU and surgical costs. These data can inform the cost-effectiveness analysis of E-CPR in the future.

Importance: Ventilator-associated pneumonia (VAP) frequently occurs in patients with cardiac arrest. Diagnosis of VAP after cardiac arrest remains challenging, while the use of current biomarkers such as C-reactive protein (CRP) or procalcitonin (PCT) is debated.

Objectives: To evaluate biomarkers' impact in helping VAP diagnosis after cardiac arrest.

Design setting and participants: This is a prospective ancillary study of the randomized, multicenter, double-blind placebo-controlled ANtibiotherapy during Therapeutic HypothermiA to pRevenT Infectious Complications (ANTHARTIC) trial evaluating the impact of antibiotic prophylaxis to prevent VAP in out-of-hospital patients with cardiac arrest secondary to shockable rhythm and treated with therapeutic hypothermia. An adjudication committee blindly evaluated VAP according to predefined clinical, radiologic, and microbiological criteria. All patients with available biomarker(s), sample(s), and consent approval were included.

Main outcomes and measures: The main endpoint was to evaluate the ability of biomarkers to correctly diagnose and predict VAP within 48 hours after sampling. The secondary endpoint was to study the combination of two biomarkers in discriminating VAP. Blood samples were collected at baseline on day 3. Routine and exploratory panel of inflammatory biomarkers measurements were blindly performed. Analyses were adjusted on the randomization group.

Results: Among 161 patients of the ANTHARTIC trial with available biological sample(s), patients with VAP (n = 33) had higher body mass index and Acute Physiology and Chronic Health Evaluation II score, more unwitnessed cardiac arrest, more catecholamines, and experienced more prolonged therapeutic hypothermia duration than patients without VAP (n = 121). In univariate analyses, biomarkers significantly associated with VAP and showing an area under the curve (AUC) greater than 0.70 were CRP (AUC = 0.76), interleukin (IL) 17A and 17C (IL17C) (0.74), macrophage colony-stimulating factor 1 (0.73), PCT (0.72), and vascular endothelial growth factor A (VEGF-A) (0.71). Multivariate analysis combining novel biomarkers revealed several pairs with p value of less than 0.001 and odds ratio greater than 1: VEGF-A + IL12 subunit beta (IL12B), Fms-related tyrosine kinase 3 ligands (Flt3L) + C-C chemokine 20 (CCL20), Flt3L + IL17A, Flt3L + IL6, STAM-binding protein (STAMBP) + CCL20, STAMBP + IL6, CCL20 + 4EBP1, CCL20 + caspase-8 (CASP8), IL6 + 4EBP1, and IL6 + CASP8. Best AUCs were observed for CRP + IL6 (0.79), CRP + CCL20 (0.78), CRP + IL17A, and CRP + IL17C.

Conclusions and relevance: Our exploratory study shows that specific biomarkers, especially CRP combined with IL6, could help to better diagnose or predict early VAP occurrence in cardiac arrest patients.

Objectives: To identify triggering receptor expressed in myeloid cells-like transcript-1 positive (TLT-1+) microparticles (MPs) and evaluate if their presence is associated with clinical outcomes and/or disease severity in acute respiratory distress syndrome (ARDS).

Design: Retrospective cohort study.

Setting: ARDS Network clinical trials.

Patients: A total of 564 patients were diagnosed with ARDS.

Interventions: None.

Measurements and main results: Using flow cytometry, we demonstrated the presence of TLT-1+ platelet-derived microparticles (PMP) that bind fibrinogen in plasma samples from fresh donors. We retrospectively quantified TLT-1, glycoprotein (Gp) 1b, or αIIbβIIIa immunopositive microparticles in plasma samples from patients with ARDS enrolled in the ARMA, KARMA, and LARMA (Studies 01 and 03 lower versus higher tidal volume, ketoconazole treatment, and lisofylline treatment Clincial Trials) ARDS Network clinical trials and evaluated the relationship between these measures and clinical outcomes. No associations were found between Gp1b+ MPs and clinical outcomes for any of the cohorts. When stratified by quartile, associations were found for survival, ventilation-free breathing, and thrombocytopenia with αIIbβIIIa+ and TLT-1+ MPs (χ2p < 0.001). Notably, 63 of 64 patients in this study who failed to achieve unassisted breathing had TLT+ PMP in the 75th percentile. In all three cohorts, patients whose TLT+ MP counts were higher than the median had higher Acute Physiology and Chronic Health Evaluation III scores, were more likely to present with thrombocytopenia and were 3.7 times (p < 0.001) more likely to die than patients with lower TLT+ PMP after adjusting for other risk factors.

Conclusions: Although both αIIbβIIIa+ and TLT+ microparticles (αIIbβIIIa, TLT-1) were associated with mortality, TLT-1+ MPs demonstrated stronger correlations with Acute Physiology and Chronic Health Evaluation III scores, unassisted breathing, and multiple system organ failure. These findings warrant further exploration of the mechanistic role of TLT-1+ PMP in ARDS or acute lung injury progression.

Importance: COVID-19 may injure the kidney tubules via activation of inflammatory host responses and/or direct viral infiltration. Most studies of kidney injury in COVID-19 lacked contemporaneous controls or measured kidney biomarkers at a single time point.

Objectives: To better understand mechanisms of acute kidney injury in COVID-19, we compared kidney outcomes and trajectories of tubular injury, viability, and function in prospectively enrolled critically ill adults with and without COVID-19.

Design, setting, and participants: The COVID-19 Host Response and Outcomes study prospectively enrolled patients admitted to ICUs in Washington State with symptoms of lower respiratory tract infection, determining COVID-19 status by nucleic acid amplification on arrival.

Main outcomes and measures: We evaluated major adverse kidney events (MAKE) defined as a doubling of serum creatinine, kidney replacement therapy, or death, in 330 patients after inverse probability weighting. In the 181 patients with available biosamples, we determined trajectories of urine kidney injury molecule-1 (KIM-1) and epithelial growth factor (EGF), and urine:plasma ratios of endogenous markers of tubular secretory clearance.

Results: At ICU admission, the mean age was 55 ± 16 years; 45% required mechanical ventilation; and the mean serum creatinine concentration was 1.1 mg/dL. COVID-19 was associated with a 70% greater occurrence of MAKE (relative risk 1.70; 95% CI, 1.05-2.74) and a 741% greater occurrence of KRT (relative risk 7.41; 95% CI, 1.69-32.41). The biomarker cohort had a median of three follow-up measurements. Urine EGF, secretory clearance ratios, and estimated glomerular filtration rate (eGFR) increased over time in the COVID-19 negative group but remained unchanged in the COVID-19 positive group. In contrast, urine KIM-1 concentrations did not significantly change over the course of the study in either group.

Conclusions: Among critically ill adults, COVID-19 is associated with a more protracted course of proximal tubular dysfunction and reduced eGFR despite similar degrees of kidney injury.

Context: Amid the COVID-19 pandemic, this study delves into ventilator shortages, exploring simple split ventilation (SSV), simple differential ventilation (SDV), and differential multiventilation (DMV). The knowledge gap centers on understanding their performance and safety implications.

Hypothesis: Our hypothesis posits that SSV, SDV, and DMV offer solutions to the ventilator crisis. Rigorous testing was anticipated to unveil advantages and limitations, aiding the development of effective ventilation approaches.

Methods and models: Using a specialized test bed, SSV, SDV, and DMV were compared. Simulated lungs in a controlled setting facilitated measurements with sensors. Statistical analysis honed in on parameters like peak inspiratory pressure (PIP) and positive end-expiratory pressure.

Results: Setting target PIP at 15 cm H2O for lung 1 and 12.5 cm H2O for lung 2, SSV revealed a PIP of 15.67 ± 0.2 cm H2O for both lungs, with tidal volume (Vt) at 152.9 ± 9 mL. In SDV, lung 1 had a PIP of 25.69 ± 0.2 cm H2O, lung 2 at 24.73 ± 0.2 cm H2O, and Vts of 464.3 ± 0.9 mL and 453.1 ± 10 mL, respectively. DMV trials showed lung 1's PIP at 13.97 ± 0.06 cm H2O, lung 2 at 12.30 ± 0.04 cm H2O, with Vts of 125.8 ± 0.004 mL and 104.4 ± 0.003 mL, respectively.

Interpretation and conclusions: This study enriches understanding of ventilator sharing strategy, emphasizing the need for careful selection. DMV, offering individualization while maintaining circuit continuity, stands out. Findings lay the foundation for robust multiplexing strategies, enhancing ventilator management in crises.

Objectives: In critically ill children with severe sepsis, septic cardiomyopathy (SCM) denotes the subset of patients who have myocardial dysfunction with poor response to fluid and inotropic support, and higher mortality risk. The objective of this review was to evaluate the role of speckle-tracking echocardiography (STE) in the diagnosis and prognosis of pediatric SCM in the PICU setting.

Data sources: We performed detailed searches using PubMed, Scopus, Web of Science, and Google Scholar. Reference lists of all included studies were also examined for further identification of potentially relevant studies.

Study selection: Studies with the following medical subject headings and keywords were selected: speckle-tracking echocardiography, strain imaging, global longitudinal strain, echocardiography, sepsis, severe sepsis, septic shock, septic cardiomyopathy, and myocardial dysfunction.

Data extraction: The following data were extracted from all included studies: demographics, diagnoses, echocardiographic parameters, severity of illness, PICU management, and outcomes.

Data synthesis: STE is a relatively new echocardiographic technique that directly quantifies myocardial contractility. It has high sensitivity in diagnosing SCM, correlates well with illness severity, and has good prognosticating value as compared with conventional echocardiographic parameters. Further studies are required to establish its role in evaluating biventricular systolic and diastolic dysfunction, and to investigate whether it has a role in individualizing treatment and improving treatment outcomes in this group of patients.

Conclusions: STE is a useful adjunct to conventional measures of cardiac function on 2D-echocardiography in the assessment of pediatric SCM in the PICU.

Objectives: While cytokine response patterns are pivotal in mediating immune responses, they are also often dysregulated in sepsis and critical illness. We hypothesized that these immunological deficits, quantifiable through ex vivo whole blood stimulation assays, may be indicative of subsequent organ dysfunction.

Design: In a prospective observational study, adult septic patients and critically ill but nonseptic controls were identified within 48 hours of critical illness onset. Using a rapid, ex vivo assay based on responses to lipopolysaccharide (LPS), anti-CD3/anti-CD28 antibodies, and phorbol 12-myristate 13-acetate with ionomycin, cytokine responses to immune stimulants were quantified. The primary outcome was the relationship between early cytokine production and subsequent organ dysfunction, as measured by the Sequential Organ Failure Assessment score on day 3 of illness (SOFAd3).

Setting: Patients were recruited in an academic medical center and data processing and analysis were done in an academic laboratory setting.

Patients: Ninety-six adult septic and critically ill nonseptic patients were enrolled.

Interventions: None.

Measurements and main results: Elevated levels of tumor necrosis factor and interleukin-6 post-endotoxin challenge were inversely correlated with SOFAd3. Interferon-gamma production per lymphocyte was inversely related to organ dysfunction at day 3 and differed between septic and nonseptic patients. Clustering analysis revealed two distinct immune phenotypes, represented by differential responses to 18 hours of LPS stimulation and 4 hours of anti-CD3/anti-CD28 stimulation.

Conclusions: Our rapid immune profiling technique offers a promising tool for early prediction and management of organ dysfunction in critically ill patients. This information could be pivotal for early intervention and for preventing irreversible organ damage during the acute phase of critical illness.

Objectives: Although clinicians may use methylene blue (MB) in refractory septic shock, the effect of MB on patient-important outcomes remains uncertain. We conducted a systematic review and meta-analysis to investigate the benefits and harms of MB administration in patients with septic shock.

Data sources: We searched six databases (including PubMed, Embase, and Medline) from inception to January 10, 2024.

Study selection: We included randomized clinical trials (RCTs) of critically ill adults comparing MB with placebo or usual care without MB administration.

Data extraction: Two reviewers performed screening, full-text review, and data extraction. We pooled data using a random-effects model, assessed the risk of bias using the modified Cochrane tool, and used Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates.

Data synthesis: We included six RCTs (302 patients). Compared with placebo or no MB administration, MB may reduce short-term mortality (RR [risk ratio] 0.66 [95% CI, 0.47-0.94], low certainty) and hospital length of stay (mean difference [MD] -2.1 d [95% CI, -1.4 to -2.8], low certainty). MB may also reduce duration of vasopressors (MD -31.1 hr [95% CI, -16.5 to -45.6], low certainty), and increase mean arterial pressure at 6 hours (MD 10.2 mm Hg [95% CI, 6.1-14.2], low certainty) compared with no MB administration. The effect of MB on serum methemoglobin concentration was uncertain (MD 0.9% [95% CI, -0.2% to 2.0%], very low certainty). We did not find any differences in adverse events.

Conclusions: Among critically ill adults with septic shock, based on low-certainty evidence, MB may reduce short-term mortality, duration of vasopressors, and hospital length of stay, with no evidence of increased adverse events. Rigorous randomized trials evaluating the efficacy of MB in septic shock are needed.

Registration: Center for Open Science (https://osf.io/hpy4j).

Importance: Microvascular autoregulation (MA) maintains adequate tissue perfusion over a range of arterial blood pressure (ABP) and is frequently impaired in critical illness. MA has been studied in the brain to derive personalized hemodynamic targets after brain injury. The ability to measure MA in other organs is not known, which may inform individualized management during shock.

Objectives: This study determines the feasibility of measuring MA in skeletal muscle using near-infrared spectroscopy (NIRS) as a marker of tissue perfusion, the derivation of optimal mean arterial pressure (MAPopt), and comparison with indices from the brain.

Design: Prospective observational study.

Setting: Medical and surgical ICU in a tertiary academic hospital.

Participants: Adult critically ill patients requiring vasoactive support on the first day of ICU admission.

Main outcomes and measures: Fifteen critically ill patients were enrolled. NIRS was applied simultaneously to skeletal muscle (brachioradialis) and brain (frontal cortex) while ABP was measured continuously via invasive catheter. MA correlation indices were calculated between ABP and NIRS from skeletal muscle total hemoglobin (MVx), muscle tissue saturation index (MOx), brain total hemoglobin (THx), and brain tissue saturation index (COx). Curve fitting algorithms derive the MAP with the lowest correlation index value, which is the MAPopt.

Results: MAPopt values were successfully calculated for each correlation index for all patients and were frequently (77%) above 65 mm Hg. For all correlation indices, median time was substantially above impaired MA threshold (24.5-34.9%) and below target MAPopt (9.0-78.6%). Muscle and brain MAPopt show moderate correlation (MVx-THx r = 0.76, p < 0.001; MOx-COx r = 0.69, p = 0.005), with a median difference of -1.27 mm Hg (-9.85 to -0.18 mm Hg) and 0.05 mm Hg (-7.05 to 2.68 mm Hg).

Conclusions and relevance: This study demonstrates, for the first time, the feasibility of calculating MA indices and MAPopt in skeletal muscle using NIRS. Future studies should explore the association between impaired skeletal muscle MA, ICU outcomes, and organ-specific differences in MA and MAPopt thresholds.

Background: Tracheostomy-related acquired pressure injuries (TRPIs) are one of the hospital-acquired conditions. We hypothesize that an uneven ventilator circuit load, leading to non-neutral tracheostomy tube positioning in the immediate post-tracheostomy period, leads to an increased incidence of TRPIs. Does switching the ventilator circuit load daily, in addition to standard post-tracheostomy care, lead to a decreased incidence of TRPIs?

Methods: This is a prospective quality improvement study. Study was conducted at two academic hospital sites within tertiary care hospitals at Emory University in different ICUs. Consecutive patients undergoing bedside percutaneous tracheostomy by the interventional pulmonary service were included. The flip the ventilator circuit (FLIC) protocol was designed and implemented in selected ICUs, with other ICUs as controls.

Results: Incidence of TRPI in intervention and control group were recorded at post-tracheostomy day 5. A total of 99 patients were included from October 22, 2019, to May 22, 2020. Overall, the total incidence of any TRPI was 23% at post-tracheostomy day 5. Incidence of stage I, stage II, and stages III-IV TRPIs at postoperative day 5 was 11%, 12%, and 0%, respectively. There was a decrease in the rate of skin breakdown in patients following the FLIC protocol when compared with standard of care (13% vs. 36%; p = 0.01). In a multivariable analysis, interventional group had decreased odds of developing TRPI (odds ratio, 0.32; 95% CI, 0.11-0.92; p = 0.03) after adjusting for age, albumin, body mass index, diabetes mellitus, and days in hospital before tracheostomy.

Conclusions: The incidence of TRPIs within the first week following percutaneous tracheostomy is high. Switching the side of the ventilator circuit to evenly distribute load, in addition to standard bundled tracheostomy care, may decrease the overall incidence of TRPIs.